The investigations described in this proposal aim at the extension and further exploration of the application of oxygen-17 nuclear magnetic resonance (nmr) spectroscopy to the elucidation of peptide structure and conformation in solution and the evaluation of the dynamics of their molecular motions by complementary studies of solute and solvent molecules. These studies will be facilitated: a. by chemical synthesis incorporating oxygen-17 at selective and specific carbonyl, carboxyl and hydroxyl groups of amino acids, peptides, and solvent molecules. b. by studies at high magnetic fields (42G and higher) and by the use of large bore probes (3 in. diameter). c. by the use of high rf power instrumentation (1 KW) designed for 17O studies of narrow as well as wide lines (10,000Hz) and large spectral widths (0.5 MHz). Conformational features, molecular dynamics and solute-solvent interactions will be investigated by measurement of the chemical shift, spin lattice and spin-spin nuclear relaxation times and by variation of pulse repetition rate. Complementary 15N, 14N, 1H, 2H and 13C nmr studies will be performed when required to more fully characterize molecular structure and dynamics of motion and to complete the 17O picture. The role of hydrogen bonded states (non-hydrogen bonded, inter- and intramolecular hydrogen bonded) in determining the conformation and molecular motion of peptides in solution, and the binding of metal ions and solvation of the peptide bond and of the amino hydroxyl and carboxyl groups, will be studied in model compounds and in peptides of biological interest as a function of temperature, solute concentration, pH and solvent composition. Thermodynamic and kinetic parameters characterizing internal modes of motion of "quasi" rigid molecules, the formation and rupture of hydrogen bonds within the peptide and with the solvent, ion binding and solvation will be determined. The long term goals of this proposal are to elucidate the relationship between three dimensional structure and biological activity of peptide hormones, CNS active agents, toxins and ionophores, as part of an effort to understand molecular processes in biological regulation and their pathology, and to assist in the design of drugs to overcome related diseases.